مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال شصت و هشتم شماره 11 (پیاپی 119، بهمن 1389)

Recombinant tissue plasminogen activator (rt-PA) is one of the most important thrombolytic agents used in patients with vascular occlusions such as acute ischemic stroke or myocardial infarction. A variety of recombinant protein expression systems have been developed for heterologous gene expression in prokaryotic and eukaryotic hosts. In recent years, Leishmania tarentolae (L. tarentolae), a non-pathogenic trypanosomatid protozoa, has come under consideration because of its safety and immunogenicity as a vaccine vector and special attributes in the expression of complex proteins. This study was done to improve rt-PA expression in this protozoon and create the opportunity for the replacement of rt-PA gene with other genes for the production of other complex proteins.

Two expression cassettes were used for the integration of two copies of t-PA cDNA, one copy in each cassette, into the parasite genome by electroporation. The transformed clones were selected by antibiotic resistancy. The expression of active secreted rt-PA was confirmed by Western blot analysis and Chromolize assay.

Appearance of a 64 kD band in nitrocellulose membrane in the Western blot analysis confirmed the presence of full-length rt-PA in the culture media. Chromolize assay showed the expression levels of active recombinant t-PA in single and double transfected L. tarentolae clones- 375 IU/ml and 480 IU/ml of the culture media, respectively.

The produced rt-PA in the culture media containing the transfected cells was at least seven times higher than what has been reported in previous studies on L. tarentolae or on some other eukaryotic systems.

Studying the behavior of a society of neurons, extracting the communication mechanisms of brain with other tissues, finding treatment for some nervous system diseases and designing neuroprosthetic devices, require an algorithm to sort neuralspikes automatically. However, sorting neural spikes is a challenging task because of the low signal to noise ratio (SNR) of the spikes. The main purpose of this study was to design an automatic algorithm for classifying neuronal spikes that are emitted from a specific region of the nervous system. The spike sorting process usually consists of three stages: detection, feature extraction and sorting. We initially used signal statistics to detect neural spikes. Then, we chose a limited number of typical spikes as features and finally used them to train a radial basis function (RBF) neural network to sort the spikes. In most spike sorting devices, these signals are not linearly discriminative. In order to solve this problem, the aforesaid RBF neural network was used. After the learning process, our proposed algorithm classified any arbitrary spike. The obtained results showed that even though the proposed Radial Basis Spike Sorter (RBSS) reached to the same error as the previous methods, however, the computational costs were much lower compared to other algorithms. Moreover, the competitive points of the proposed algorithm were its good speed and low computational complexity. Regarding the results of this study, the proposed algorithm seems to serve the purpose of procedures that require real-time processing and spike sorting.

Exogenous natural and synthetic surfactants is a rescue treatment for respiratory distress syndrome (RDS). The goals of the study were to compare the clinical response and side-effects of two frequently used surfactants, poractant alfa (Curosurf) and beractant (Survanta), for the treatment of respiratory distress syndrome in preterm infants.

This clinical trial study was performed during a two-year period in the Neonatal Intensive Care Unit of Ghaem Hospital in Mashhad, Iran. Sample size calculated by a 95% confidence and power of 80, included 104 premature neonates, 74 in survanta and 30 in curosurf groups. The level of statistical significance was considered to be < 0.05

There were no statistically significant differences between the infants treated by survanta or cursurf groups regarding their mean gestational age (30.58 Vs. 29.00 weeks) and birth weight (1388 Vs. 1330 g), (p=0.3) There were also no significant differences between the two groups regarding incidences of broncho- pulmonary dysplasia (BPD) (40.5% Vs. 40%), intraventricular hemorrhage (IVH) grades III/IV (13.5% Vs. 13.3%), pneumothorax (both 20%), patent ductus arteriosus (PDA) (28/3% Vs. 20%) or death (28% Vs. 26.6%) on the 28th day postpartum.

This study showed that survanta and curosurf had similar therapeutic effects in the treatment of neonatal respiratory distress syndrome.

Many chemotherapeutic regimens used in the treatment of cancer generate free radicals that may be a part of their beneficial effects. The aim of this study was to assess the oxidative status in patients undergoing chemotherapy for acute myeloid leukemia (AML). Thirty-eight patients with AML (17 female and 21 male patients) with a mean age 34.05±12.49 years were included in the study. All the patients received cytarabine and daunorubicin as their standard induction therapy. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and also the erythrocyte superoxide dismutase and glutathione peroxidase activities were measured before and 14 days after chemotherapy. Plasma malondialdehyde concentrations increased significantly (from a former 2.68±0.89 nmol/ml to 3.14±1.29 nmol/ml) 14 days post chemotherapy (p=0.04). Moreover, the total plasma antioxidant capacity changed from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L (p=0.005). Erythrocyte superoxide dismutase and glutathione peroxidase activity decreased over time from 1157.24±543.61 U/gHb to 984.01±419.09 U/gHb (p=0.04) and 46.96±13.70 U/gHb to 41.40±6.44 U/gHb (p=0.02), respectively. In this study, an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant capacity were observed. It seems that chemotherapy by cytarabine and daunorubicin generates enormous amounts of free radicals in patients undergoing the treatment for AML. Use of antioxidant supplementation during chemotherapy i is discouraged as it may interfere with the generation of free radicals that may be a part of the therapeutic efficacy of these drugs.

Vitiligo is a common acquired disorder characterized by depigmented cutaneous patches devoid of melanocytes. The disease carries a risk for ocular abnormalities. Few reports are available about the ocular findings and their possible association with the disease in patients with vitiligo in the literature. A total of 72 patients with previously documented cutaneous vitiligo were examined for ocular findings and 50 healthy individuals were enrolled as the control group in Razi Hospital in Tehran, Iran during years 2007-2008. Demographic features including age, gender, duration of the disease, presence of any accompanying autoimmune diseases, type of vitiligo and its anatomical distribution were recorded to investigate a possible association between the disease and the ocular findings. Amongst 72 patients with vitiligo, 11 (15.3%) had ocular findings including retinal pigment epithelium hypopigmentation, posterior pole pigment changes, peripheral iris atrophy, atrophy of retinal pigment epithelium and iris hyperpigmentation. Amongst the controls, only two cases (4%) had ocular findings which consisted of iris hyperpigmentation. The relationship between ocular findings and vitiligo was statistically significant (p= 0.04). No other remarkable features, such as age, gender, age at the onset of the disease, type of vitiligo, presence of priorbital lesions or body surface area involvement by the disease, were suggestive of an association or presenting a risk factor for vitiligo. Although the sample size and prevalence of ocular findings were not satisfactory enough to make a definite conclusion, we found a higher occurrence of ocular findings in patients with vitiligo than the control group.

Asthma is a life-threatening disease that can cause death due to bronchospasm. In addition to clinical symptoms such as wheezing, acute paroxysmal dyspnea, chronic cough after exposure to cold air or cough after exercise, spirometry is also necessary for the diagnosis of asthma. The association between respiratory symptoms and a positive methacholine challenge test (MCT) is still controversial. The aim of this study was to determine the association between methacholine test results and respiratory symptoms and allergy. One hundred and forty-six patients with respiratory symptoms and normal baseline pulmonary function tests were enrolled in this cross-sectional study. The participants were divided into two groups according to their positive or negative response to MCT. The association between MCT and the clinical symptoms and allergy was later evaluated statistically. Out of 146 participants of the study 59 (40.4%) were female and 87 (59.6%) were male. The mean age of the participants was 33.8±13.8 years. Sixty-one patients (41.8%) had positive results for the test. There was an association between a history of allergy, wheezing and age with positive MCT results. The other clinical signs had no association with the test. Methacholine challenge test is the best diagnostic test for ruling out asthma in patients with normal pulmonary function tests in whom we cannot definitely rule out asthma based solely on clinical symptoms. Nevertheless, in adults with a history of allergy, wheezing and also in patients below 30, the probability for a positive MCT is high.

Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating from the lung or thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers in this regard.

Thirteen endocervical adenocarcinomas, 39 endometrioid endometrial adenocarcinomas and four uterine serous carcinomas which had no neuroendocrine component were retrieved, stained by TTF-1 and examined. A semiquantitative grading system was used to evaluate the distribution of TTF-1 staining (0= negative, 1+  5%, 2+= 5% to 25%, 3+= 26% to 50%, 4+= 51% to 75% and 5+  75%). A qualitative system was also used to evaluate the intensity of TTF-1 staining (weak, moderate and strong).

TTF-1 expression was seen in 1 out of 13 (7.7%) endocervical adenocarcinoma samples, showing 1+ distribution rate and weak intensity. The positive sample was moderately differentiated. TTF-1 expression was present in 2 out of 39 (5.1%) endometrioid adenocarcinoma samples (one grade I and the other grade II) with 1+ distribution rate and weak intensity. There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the studied adenocarcinomas. None of the four endometrial serous carcinomas were positive for TTF-1.

Although some recent studies cast doubt about the specificity of TTF-1 for lung and thyroid carcinoma, our study showed that TTF-1 was negative in endocervical and endometrial adenocarcinomas and established the specificity of TTF-1 for lung and thyroid carcinomas.

Diabetes is a chronic non-communicable disease with increasing prevalence. Retinopathy is one of the main complications of diabetes. Early diagnosis and treatment of retinopathy can reduce the risk of low vision and blindness. The aim of this study was to apply regression analysis of current status data to determine risk factors of diabetic retinopathy in patients with type 2 diabetes being referred to the Ophthalmology Clinic of Yazd Diabetes Research Center, Iran. In this analytical-observational study, 459 patients with type 2 diabetes were enrolled in the study and the ophthalmic examinations done by an ophthalmologist included visual acuity, intraocular pressure (IOP) measurement and slit-lamp examination. After pupil dilatation, funduscopy was done and the patients were classified according to ETDRS criteria. A proportional hazard model for current status data was used to identify the risk factors for retinopathy. The hazard rate of having retinopathy increased by 5% for an increase of one year in the duration of diabetes (p<0.05) and the hazard rate of having retinopathy was 1.1 times greater in patients who had used insulin for diabetes compared with other type 2 diabetes patients (p<0.05). This study showed that a history of hypertension may reduce the risks of diabetic retinopathy. In patients with the early diagnosis of diabetes, regular examination of the fundus, blood sugar control and tight control of high blood pressure are recommended.

Prohepcidin, a liver-derived peptide with antimicrobial properties, is regulated by factors such as iron load and inflammation. Hepcidin is a central player in iron homeostasis. It downregulates the iron exporter ferroportin, thereby inhibiting iron absorption, release and recycling. Thus, prohepcidin increases the possibility of iron-limited erythropoiesis and development of anemia. In end-stage renal disease (ESRD), plasma hepcidin levels are elevated, which may contribute to iron deficiency in these patients. This study was undertaken to investigate the relationship between prohepcidin and serum biochemical parameters related to anemia and inflammation in the aforesaid patients.

Fifty-four stable patients with uremia who were on chronic hemodialysis were enrolled in the study. The patients were withheld from intravenous iron two weeks prior to laboratory measurements. Later, (total) prohepcidin was measured by ELISA method as were other parameters including serum iron, TIBC, TSAT, Hct, ferritin, albumin, CRP, ESR, cholesterol and triglyceride.

Serum prohepcidin levels were higher than normal values in the patients, but they were not correlated to the serum iron, TIBC, TSAT, Hct, ferritin, albumin, cholesterol and triglyceride (p>0.05). No significant association were also found with ESR (p=0.97, r= -0.005) or CRP (p=0.053, r =0.26).

Serum prohepcidin level was higher in chronic hemodialysis patients but it was not predictive of iron status or inflammatory conditions in these patients. Confirmation of these results may necessitate studies with larger sample sizes or measurement of the biologically active form of hepcidin.

Simple cysts of pancreas are smaller than complex ones and are more likely to be located at the distal tail of the pancreas. Simple cysts are often asymptomatic and can be managed conservatively by observation. There seems to be few clinical trials to suggest the best treatments method for large symptomatic cysts of pancreas located at the head of the organ.

In this report, we describe an eight-year old boy with a large symptomatic true cyst at the head of the pancreas who was successfully treated by enucleation of the cyst, instead of the Whipple's procedure, without any ensuing complications.

Regarding the rarity of simple cysts in the pancreas, lack of studies to compare different surgical procedures and suggest the best methods to treat them and the considerable morbidity and even mortality of major surgeries (e.g Whipple's procedure) enucleation of these cysts seem to be appropriate for treating them with no early or late complications. More studies are needed to warrant the results of this report.